Accumulating evidence implicates interleukin-8 (IL-8) as an essential mediator in neutrophil-mediated acute inflammation. Neutrophils have also been shown to have a crucial role in the pathogenesis of acute gouty arthritis. Thus, we investigate the pathophysiological role of IL-8 in an experimental model of acute gout, monosodium urate (MSU) crystal-induced arthritis in rabbits. The injection of MSU crystals into knee joints caused a marked swelling of joints. Concomitantly, the infiltration ofleukocytes, mostly neutrophils, was observed in synovial membrane and synovial fluids. The injection of MSU crystals also induced an elevation in synovial fluid IL-8 levels preceding neutrophil infiltration into synovial fluids, without an accompanying increase in plasma IL-8 levels. Immunoreactive IL-8 protein was detected in synovial lining cells at 12-24 h after the injection. IL-8 protein was also observed in infiltrated leukocytes in synovium as early as 3-24 h after the injection. Finally, the intraarticular injection of a neutralizing anti-IL-8 antibody significantly attenuated the crystal-induced joint swelling that occurred at 12 h, and neutrophil infiltration into arthritic joints at 12 and 24 h after the induction. These results provide evidence on the pathogenic roles of locally produced IL-8 in MSU crystal-induced gouty arthritis.
Objective. Peroxisome proliferator-activated receptor ␥ (PPAR␥) is a member of the nuclear hormone receptor superfamily and functions as a key regulator of lipid and glucose metabolism, atherosclerosis, and inflammatory responses. This study was undertaken to evaluate the biologic role of PPAR␥ in self-limiting episodes of acute gouty arthritis. To do this, we investigated PPAR␥ expression by monosodium urate monohydrate (MSU) crystal-stimulated monocytes, and we studied the effects of PPAR␥ ligands on crystal-induced acute inflammation.Methods. PPAR␥ expression by MSU crystalstimulated human peripheral blood mononuclear cells was determined by reverse transcription-polymerase chain reaction and immunostaining. Expression of CD36 on monocytes was detected by flow cytometric analysis. The effects of PPAR␥ ligands on in vitro crystal-induced cytokine production and on in vivo cellular infiltration during crystal-induced acute inflammation were also investigated.Results. MSU crystals rapidly and selectively induced PPAR␥ expression by monocytes. Gene expression was detected as early as 2 hours, and maximum expression was observed at 4 hours after stimulation. The induced PPAR␥ was functional, since a PPAR␥ ligand was able to up-regulate CD36 expression on monocytes. A natural ligand of PPAR␥, 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15deoxy-PGJ 2 ), significantly reduced the crystal-induced production of cytokines by monocytes. Indomethacin inhibited cytokine production only at high concentrations, and an antidiabetic thiazolidinedione (troglitazone) failed to exert significant effects. Administration of troglitazone and 15deoxy-PGJ 2 significantly prevented cellular accumulation in a mouse air-pouch model of MSU crystal-induced acute inflammation.Conclusion. Rapid induction of PPAR␥ expression on monocytes by MSU crystals may contribute, at least in part, to the spontaneous resolution of acute attacks of gout.
SUMMARY To determine the roles of IL‐8 in inflammatory synovitis. examination was made of the results of continuously injecting human recombinant IL‐8 into the knee joints of New Zealand white rabbits. Recombinant human lL‐8 was infused continuously into the joint cavity at 75 ng/h for 14 days by a polypropylene catheter connected to a mini‐osmotic pump implanted in each rabbit. Infiltration of inflammatory cells into joint cavity and histopathological changes in synovial tissue were examined at 7 and 14 days following the start of infusion. The continuous infusion of IL‐8 for 14days led to severe arthritis characterized by apparent erythema and joint pain, the accumulation of leucocytes, infiltration of mononuclear cells in synovial tissue, and marked hypervascularization in the synovial lining layer. IL‐8 may be a factor which can contribute to the inflammatory process of chronic arthritis by mediating leucocyte recruitment and hypervascularization in inflamed joints.
Bilateral shoulder joint disorders caused by rheumatoid arthritis significantly impair daily functioning owing to a lack of contralateral compensation. In Japan, reverse shoulder joint prostheses were approved in 2014. This was expected to improve the surgical outcomes of rheumatoid shoulder arthroplasty. We report two patients with rheumatoid arthritis who underwent bilateral reverse shoulder arthroplasty. This study aims to evaluate their postoperative clinical outcomes and activities of daily living. The patients were women in their 70s with stage III class 2 rheumatoid arthritis. Their treatment and postoperative activities of daily living were retrospectively reviewed. The first patient underwent the inlay type and experienced a residual limitation of external rotation postoperatively; therefore, she was restricted to dress with front-open clothes. However, she was able to undress after the lining of the garment was changed to a slippery material. The second patient underwent the onlay type and showed almost no limitations in postoperative activities of daily living. She was able to undress with an external rotation of 40–50°. Bilateral reverse shoulder arthroplasty improved range of motion, the Japanese Orthopaedic Association shoulder score, and functional outcomes. Only a few difficulties were encountered in the activities of daily living.
Objective: Treatment options for patients with rheumatoid arthritis on maintenance hemodialysis with an inadequate response to biologic agents have not been reported. In this report, we describe two patients who achieved remission after treatment with peficitinib. Methods: Two 69-and 85-year-old patients with rheumatoid arthritis on maintenance hemodialysis were previously treated with biologics and started on peficitinib 100 mg/day after the secondary failure of biologics. Discussion: In the two cases presented here, rheumatoid arthritis was almost in remission and there were no adverse events, although the patients were switched to peficitinib after secondary failure of the biologic agents. Among Janus kinase inhibitors, peficitinib has the lowest renal excretion; therefore, its administration in patients on dialysis is not contraindicated according to the package insert in Japan. The use of biologic agents in patients on hemodialysis has been reported to be associated with a high incidence of infections; therefore, care should be taken to avoid infections when administering Janus kinase inhibitors. Conclusion: Janus kinase inhibitors with low renal excretion, such as peficitinib, may be effective in patients with rheumatoid arthritis on maintenance hemodialysis who have an inadequate response to biologic agents.
Dynamic magnetic resonance imaging (dynamic MRI) was used to examine the synovial membrane in the knee joints of 15 patients with rheumatoid arthritis (RA) in order to investigate the relationship between pathological and MRI findings. Signal intensities in the regions of interest (ROI), identified as the synovial membrane of the suprapatellar pouch, were measured on MR images. Signal intensities at various times after the injection of contrast medium Gd-diethylenetriaminopentoacetic acid (Gd-DTPA) were normalized relative to the signal intensity at 80 s, and designated as the normalized signal intensity (NSI). Pathological findings were quantified, and the types of inflamed synovial membrane were classified as either acute or chronic. A significant difference in NSI was observed between acute and chronic types (P < 0.05). Dynamic MRI was capable of classifying acute and chronic RA by measuring NSI 20 s after contrast medium injection. Dynamic MRI was therefore shown to be useful for assessing regional synovial inflammation.
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